ACE inhibition with perindopril and biomarkers of atherosclerosis and thrombosis: results from the PERTINENT study.
The PERTINENT study measured biomarkers of atherosclerosis and thrombosis in a stable coronary artery disease population from EUROPA receiving ACE inhibition with perindopril 8 mg/day or placebo. Biomarkers of inflammation, C-reactive protein (CRP), fibrinogen, and tumor necrosis factor-alpha (TNF-alpha), and a biomarker of thrombosis, D-dimer, were measured at baseline and 1 year. CRP was recorded in 1157 patients; fibrinogen, TNF-alpha, and D-dimer in 291 patients. There was no significant effect of treatment on CRP or fibrinogen. In contrast, there were significant reductions in TNF-alpha (27.60-25.20 pg/mL; P<0.05) and D-dimer (0.24-0.18 microg/mL; P<0.05) with perindopril over 1 year. Survival analysis of the prognostic significance of baseline CRP failed to detect a significant role for the prediction of cardiovascular events over 4 years (lower versus higher tertile: 1.54; 95% confidence interval 0.88-2.68; P=0.16). In conclusion, in the PERTINENT trial, we observed significant effects of ACE inhibition on biomarkers of the atherothrombotic complications (D-dimer) and the proinflammatory cytokine TNF-alpha, but not on biomarkers of inflammation associated with atherosclerosis (CRP and fibrinogen).
Ceconi
Claudio
C
University of Ferrara, Salvatore Maugeri Foundation, IRCCS, Ferrara, Italy. claudio.ceconi@unife.it
Fox
Kim M
KM
Remme
William J
WJ
Simoons
Maarten L
ML
Deckers
Jaap W
JW
Bertrand
Michel
M
Parrinello
Giovanni
G
Kluft
Cornelius
C
Blann
Andrew
A
Cokkinos
Dennis
D
Ferrari
Roberto
R
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D003328:Coronary Thrombosis / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D005060:Europe; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D018836:Inflammation Mediators / Q000097:blood*; D053208:Kaplan-Meier Estimate; D020913:Perindopril / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; C036309:fibrin fragment D; D005340:Fibrinogen; D002097:C-Reactive Protein; D020913:Perindopril